Phase I clinical and pharmacologic study of the focal adhesion kinase (FAK) inhibitor GSK2256098 in pts with advanced solid tumors.

3000 Background: FAK has an important role in cancer invasion and metastasis. FAK and phospho-FAK (pFAK) are increased in advanced cancer and are correlated with poor prognosis. GSK2256098 is a potent and specific small molecule inhibitor of FAK. Methods: This is a first-time in cancer pts, dose escalation study (NCT01138033) to identify the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity. Part 1 used a modified accelerated titration procedure switching to standard 3+3 design based on toxicity during the first 21 days of treatment. Pts were treated with GSK2256098 orally twice daily (BID) with food. Safety was established in cohorts of 1-6 pts. After MTD determination, Parts 2 and 3 were opened to further evaluate safety, PK and PD. Serial PK samples were obtained over 24 h on Days 1 and 15. Pre- and post-dose skin, hair and tumor tissue biopsies were analyzed for pFAK. Results: 57 pts with advanced solid tumors have been treated at escalating dose...